Caveolin-1 tumor-promoting role in human melanoma.
Caveolin-1 tumor-promoting role in human melanoma.
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DOI：
10.1002/ijc.24451
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发表时间：
2009-10-01
影响因子：
6.4
通讯作者：
Carè A
中科院分区：
文献类型：
--
作者：
Felicetti F;Parolini I;Bottero L;Fecchi K;Errico MC;Raggi C;Biffoni M;Spadaro F;Lisanti MP;Sargiacomo M;Carè A
Caveolin-1 (Cav-1) 是 Caveolin 家族的成员，可调节 Caveolae 相关信号蛋白，这些蛋白参与许多生物过程，包括癌症的发展。人们发现 Cav-1 作为癌基因或肿瘤抑制基因发挥着复杂而模糊的作用，具体取决于细胞微环境。在这里，我们研究了一组黑色素瘤中的 Cav-1 表达和功能，发现其在所有细胞系中表达。例外的是原代垂直黑色素瘤细胞系 WM983A，其特征是缺乏 Cav-1，然后用作 Cav-1 基因转导的受体来进行一系列功能研究。磷酸化Cav-1对细胞调节的所谓但有争议的作用也通过转导不可磷酸化的Cav-1Y14A突变体进行了测试。野生型 Cav-1（而非突变型 Cav-1Y14A）增加了致瘤性，如在半固体培养基中增强的增殖、迁移、侵袭和形成病灶的能力所表明的。因此，Cav-1沉默抑制了黑色素瘤细胞的生长，从而减少了一些典型的恶性肿瘤特征。最后，我们检测到与细胞释放的微泡颗粒相关的 Cav-1 的分泌部分，能够以旁分泌/自分泌的方式刺激体外贴壁独立性、迁移和侵袭，更重要的是，能够将转移资产从供体黑色素瘤转移到侵袭性较低的受体细胞系。还观察到 Cav-1 水平、培养基中释放的 MV 量和 MMP-9 表达之间存在直接相关性。
Caveolin-1 (Cav-1), a member of the caveolin family, regulates caveolae-associated signaling proteins, which are involved in many biological processes, including cancer development. Cav-1 was found to exert a complex and ambiguous role as oncogene or tumor suppressor depending on the cellular microenvironment. Here we investigated Cav-1 expression and function in a panel of melanomas, finding its expression in all the cell lines. The exception was the primary vertical melanoma cell line, WM983A, characterized by the lack of Cav-1, and then utilized as a recipient for Cav-1 gene transduction to address a series of functional studies. The alleged yet controversial role of phospho-Cav-1 on cell regulation was also tested by transducing the non phosphorylatable Cav-1Y14A mutant. Wild type Cav-1, but not mutated Cav-1Y14A, increased tumorigenicity as indicated by enhanced proliferation, migration, invasion and capacity of forming foci in semisolid medium. Accordingly, Cav-1 silencing inhibited melanoma cell growth reducing some of the typical traits of malignancy. Finally, we detected a secreted fraction of Cav-1 associated with cell released microvesicular particles able to stimulate in vitro anchorage independence, migration and invasion in a paracrine/autocrine fashion and, more important, competent to convey metastatic asset from the donor melanoma to the less aggressive recipient cell line. A direct correlation between Cav-1 levels, the amount of MV released in the culture medium and MMP-9 expression was also observed.
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影响因子：
4
作者：
Hakulinen, Juha;Sankkila, Lotta;Keski-Oja, Jorma
通讯作者：
Keski-Oja, Jorma
影响因子：
4.5
作者：
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通讯作者：
Parat, Marie-Odile
影响因子：
11.2
作者：
Joshi, Bharat;Strugnell, Scott S.;Nabi, Ivan R.
通讯作者：
Nabi, Ivan R.
影响因子：
11.2
作者：
Ayala, GE;Dai, H;Thompson, TC
通讯作者：
Thompson, TC
影响因子：
21.3
作者：
Liu, PS;Li, WP;Anderson, RGW
通讯作者：
Anderson, RGW